The purpose of this EUREKA application is to develop a multi-factorial modeling tool that can provide decision- makers information on how to set foodborne aflatoxin standards that reduce global liver cancer incidence. Liver cancer (hepatocellular carcinoma) is the 3rd-leading cause of cancer deaths worldwide, with an increasing incidence that parallels the rise in chronic hepatitis B (HBV) and hepatitis C (HCV) infection. Aflatoxin is a potent hepatocarcinogen that synergizes with HBV and HCV to produce 30-fold higher liver cancer risk than either exposure alone. Aflatoxin is produced by the fungi Aspergillus flavus and A. parasiticus in maize and peanuts under warm climatic conditions. Hence, the global populations most at risk of aflatoxin-induced liver cancer are those who consume high levels of maize and peanuts, in less developed countries (LDCs) in the tropics and subtropics where resources to control aflatoxin are scarce. We hypothesize that computational modeling that simulates both public health effects and trade / economic consequences can provide unique insights into how regulatory standards can ameliorate global cancer burden. Over 100 nations have set standards on maximum allowable aflatoxin levels in food. These standards vary widely from nation to nation. Efforts are now being made to harmonize aflatoxin standards globally, to prevent world food trade disputes. We address the question: What should the harmonized aflatoxin standard be to best protect global health? Ironically, setting a very strict standard could result in more cancer cases, for 3 reasons: 1. Rich, food-importing countries would have limited health benefits because of low hepatitis prevalence, while food-exporting LDCs may incur excessive costs to meet such standards. 2. Limiting food export markets could increase poverty in LDCs, which would augment hunger and poor health conducive to increased hepatitis infection and liver cancer risk. 3. To preserve their export markets, Asian and African nations may attempt to export their best-quality food and keep the most highly contaminated food domestically, raising the risk of aflatoxin consumption and liver cancer in parts of the world that currently have the highest rates of hepatitis infection. Because conducting clinical trials is neither practical nor ethical, and retrospective data are limited, computer simulation modeling is an extremely useful technique to examine the consequences of different global aflatoxin standards on food trade and cancer incidence. A powerful attribute of the decision analytic approach to public health is the ability to evaluate several dimensions simultaneously. We seek to create an innovative modeling tool that integrates global liver cancer and hepatitis incidence, aflatoxin exposure through maize and nuts, costs, and technological changes into a single decision-analytic framework. Our specific aim is to determine the effect of selected harmonized aflatoxin standards on both global food export losses and global burden of aflatoxin-induced liver cancer, under current conditions and future scenarios. PUBLIC HEALTH RELEVANCE: Public Health Relevance Statement: As befits the purpose of EUREKA, our proposed research accelerates knowledge in a crucial time when the United Nations and the World Trade Organization are pushing to harmonize food safety standards across nations. Until now, little work has been done to assess global health impacts of harmonized standards; now, we are in a position to apply novel modeling techniques to provide that necessary knowledge to decision-makers. While we focus on the impact of a harmonized aflatoxin standard on global liver cancer burden, the methodologies can be broadened to address standard-setting of other important carcinogens.